If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Locations of Mapped Genes:
|Superclasses:||Degradation/Utilization/Assimilation → Amino Acids Degradation → Proteinogenic Amino Acids Degradation → L-threonine Degradation|
Microorganisms and mammals share two of the major, initial routes for threonine degradation. In the first route threonine is catabolized by catabolic threonine dehydratase (EC 126.96.36.199) to ammonia and 2-oxobutanoate. A biosynthetic version of this enzyme also occurs (see threonine deaminase) [Umbarger57]. In the second route threonine is catabolized by threonine dehydrogenase (EC 188.8.131.52) to form 2-amino-3-oxobutanoate, which is mainly cleaved by 2-amino-3-ketobutyrate CoA ligase, forming glycine and acetyl-CoA. The 2-amino-3-oxobutanoate can also be spontaneously converted to aminoacetone, which may be further metabolized to methylglyoxal (see L-threonine degradation III (to methylglyoxal)). A third route has been demonstrated in several bacteria and fungi. This route is based on the enzyme low-specificity L-threonine aldolase (EC 184.108.40.206), which cleaves threonine directly into glycine and acetaldehyde.
Escherichia. coli has been shown to assimilate nitrogen from some (but not all) amino acids, as well as agmatine, γ-aminobutyrate and the polyamines putrescine and spermidine. These nitrogen sources are used to generate glutamate and glutamine, the major intracellular nitrogen donors. Some nitrogen sources, such as aspartate, can generate glutamate by transamination (see aspartate aminotransferase, PLP-dependent). Others, such as proline and arginine, produce glutamate as end products (glutamate generating amino acids) (see proline degradation and L-arginine degradation II (AST pathway)). Other nitrogen sources, such as serine, require ammonia production for glutamate synthesis (ammonia generating amino acids) (see L-serine degradation). Ammonia generation is required for glutamine synthesis (see L-glutamine biosynthesis I).
In E. coli a low intracellular level of ammonia results in low intracellular glutamine and induction of the nitrogen-regulated (Ntr) response that involves response regulators NtrC transcriptional dual regulator and NtrB sensory histidine kinase. The Ntr response functions in ammonia assimilation, nitrogen scavenging and metabolic coordination.
E. coli has three systems that can transport threonine: serine / threonine:Na+ symporter [Kim02], branched chain amino acid ABC transporter [Robbins73], and serine / threonine:H+ symporter TdcC [Sumantran90]. Although E. coli can use threonine, glycine, or serine as a nitrogen source, efficient serine or threonine utilization requires amino acid supplementation. Leucine supplementation is required for the use of threonine as a nitrogen source in pathways utilizing threonine dehydrogenase (TDH) which is induced by leucine [Potter77] (see L-threonine degradation II and L-threonine degradation III (to methylglyoxal)). TDH is is a major route for threonine degradation in E. coli. A minor pathway is shown in L-threonine degradation IV and an anaerobic pathway is shown in L-threonine degradation I.
About This Pathway
Enteric bacteria such as Escherichia coli K-12 and Salmonella enterica subsp. enterica serovar Typhimurium have been shown to possess two types of threonine dehydratases - a catabolic enzyme, which is induced by threonine (see catabolic threonine dehydratase), and a constitutively-produced biosynthetic enzyme (see threonine deaminase) [Umbarger57]. Both enzymes convert threonine to 2-oxobutanoate. While the biosynthetic enzyme is involved in isoleucine biosynthesis (see L-isoleucine biosynthesis I (from threonine)), the catabolic enzyme participates in the degradation of threonine to propionate in a pathway that generates ATP and enables the utilization of threonine as a sole source of carbon and energy [Luginbuhl74]. This E. coli anaerobic threonine dehydratase pathway is shown here [Sawers98, Hesslinger98].
The first reaction in this pathway is catalyzed by catabolic threonine dehydratase which degrades threonine to 2-oxobutanoate (α-ketobutyrate) and ammonia. The 2-oxobutanoate then undergoes lyase cleavage with the addition of coenzyme A to form propanoyl-CoA and formate. Two such lyases were discovered in E. coli K-12 [Hesslinger98]. Both of these enzymes, pyruvate formate-lyase / 2-ketobutyrate formate-lyase encoded by gene pflB and 2-ketobutyrate formate-lyase / pyruvate formate-lyase 4 encoded by gene tdcE, are expressed only under anaerobic conditions, and both utilize a glycyl radical as part of their catalytic mechanism [Sawers98b]. TdcE is equally active with 2-oxobutanoate and pyruvate substrates, whereas PflB prefers pyruvate. Once propanoyl-CoA is formed, it is processed via propionyl-phosphate to propionate in a reaction sequence that produces ATP. Acetate kinase AckA can also utilize propionate as a substrate in the final reaction. The enzymes in this pathway are also able to process L-serine, with pyruvate as the final product [Sawers98].
Features of this energy-generating pathway include substrate-level phosphorylation, a requirement for cAMP-CRP, and catabolite repression. The tdcABCDEFG operon genes also encode serine / threonine:H+ symporter TdcC (see above), L-serine deaminase III, and predicted enamine/imine deaminase. Regulators of the operon include adjacent TdcR DNA-binding transcriptional activator, CRP transcriptional dual regulator, IHF DNA-binding transcriptional dual regulator, and TdcA DNA-binding transcriptional activator. This pathway does not appear to be essential because inactivation of tdcB [Goss84]. tdcE [Hesslinger98], or tdcD [Hesslinger98] resulted in no discernible phenotype.
Superpathways: superpathway of L-threonine metabolism
Bell77: Bell SC, Turner JM (1977). "Bacterial catabolism of threonine. Threonine degradation initiated by l-threonine hydrolyase (deaminating) in a species of Corynebacterium." Biochem J 164(3);579-587. PMID: 16743051
Hesslinger98: Hesslinger C, Fairhurst SA, Sawers G (1998). "Novel keto acid formate-lyase and propionate kinase enzymes are components of an anaerobic pathway in Escherichia coli that degrades L-threonine to propionate." Mol Microbiol 1998;27(2);477-92. PMID: 9484901
Kim02: Kim YM, Ogawa W, Tamai E, Kuroda T, Mizushima T, Tsuchiya T (2002). "Purification, reconstitution, and characterization of Na(+)/serine symporter, SstT, of Escherichia coli." J Biochem (Tokyo) 132(1);71-6. PMID: 12097162
Shizuta70: Shizuta Y, Hayaishi O (1970). "Regulation of biodegradative threonine deaminase synthesis in Escherichia coli by cyclic adenosine 3',5'-monophosphate." J Biol Chem 245(20);5416-23. PMID: 4319241
Simanshu07: Simanshu DK, Chittori S, Savithri HS, Murthy MR (2007). "Structure and function of enzymes involved in the anaerobic degradation of L-threonine to propionate." J Biosci 32(6);1195-206. PMID: 17954980
Arifuzzaman06: Arifuzzaman M, Maeda M, Itoh A, Nishikata K, Takita C, Saito R, Ara T, Nakahigashi K, Huang HC, Hirai A, Tsuzuki K, Nakamura S, Altaf-Ul-Amin M, Oshima T, Baba T, Yamamoto N, Kawamura T, Ioka-Nakamichi T, Kitagawa M, Tomita M, Kanaya S, Wada C, Mori H (2006). "Large-scale identification of protein-protein interaction of Escherichia coli K-12." Genome Res 16(5);686-91. PMID: 16606699
Avison01: Avison MB, Horton RE, Walsh TR, Bennett PM (2001). "Escherichia coli CreBC is a global regulator of gene expression that responds to growth in minimal media." J Biol Chem 276(29);26955-61. PMID: 11350954
Barak98: Barak R, Abouhamad WN, Eisenbach M (1998). "Both acetate kinase and acetyl coenzyme A synthetase are involved in acetate-stimulated change in the direction of flagellar rotation in Escherichia coli." J Bacteriol 1998;180(4);985-8. PMID: 9473056
Becker02: Becker A, Kabsch W (2002). "X-ray structure of pyruvate formate-lyase in complex with pyruvate and CoA. How the enzyme uses the Cys-418 thiyl radical for pyruvate cleavage." J Biol Chem 277(42);40036-42. PMID: 12163496
Becker99a: Becker A, Fritz-Wolf K, Kabsch W, Knappe J, Schultz S, Volker Wagner AF (1999). "Structure and mechanism of the glycyl radical enzyme pyruvate formate-lyase." Nat Struct Biol 6(10);969-75. PMID: 10504733
Blaschkowski82: Blaschkowski HP, Neuer G, Ludwig-Festl M, Knappe J (1982). "Routes of flavodoxin and ferredoxin reduction in Escherichia coli. CoA-acylating pyruvate: flavodoxin and NADPH: flavodoxin oxidoreductases participating in the activation of pyruvate formate-lyase." Eur J Biochem 1982;123(3);563-9. PMID: 7042345
Butland05: Butland G, Peregrin-Alvarez JM, Li J, Yang W, Yang X, Canadien V, Starostine A, Richards D, Beattie B, Krogan N, Davey M, Parkinson J, Greenblatt J, Emili A (2005). "Interaction network containing conserved and essential protein complexes in Escherichia coli." Nature 433(7025);531-7. PMID: 15690043
CamposBermudez10: Campos-Bermudez VA, Bologna FP, Andreo CS, Drincovich MF (2010). "Functional dissection of Escherichia coli phosphotransacetylase structural domains and analysis of key compounds involved in activity regulation." FEBS J 277(8);1957-66. PMID: 20236319
CastanoCerezo09: Castano-Cerezo S, Pastor JM, Renilla S, Bernal V, Iborra JL, Canovas M (2009). "An insight into the role of phosphotransacetylase (pta) and the acetate/acetyl-CoA node in Escherichia coli." Microb Cell Fact 8;54. PMID: 19852855
Chang99: Chang DE, Shin S, Rhee JS, Pan JG (1999). "Acetate metabolism in a pta mutant of Escherichia coli W3110: importance of maintaining acetyl coenzyme A flux for growth and survival." J Bacteriol 181(21);6656-63. PMID: 10542166
Conradt84: Conradt H, Hohmann-Berger M, Hohmann HP, Blaschkowski HP, Knappe J (1984). "Pyruvate formate-lyase (inactive form) and pyruvate formate-lyase activating enzyme of Escherichia coli: isolation and structural properties." Arch Biochem Biophys 1984;228(1);133-42. PMID: 6364987
Datta87: Datta P, Goss TJ, Omnaas JR, Patil RV (1987). "Covalent structure of biodegradative threonine dehydratase of Escherichia coli: homology with other dehydratases." Proc Natl Acad Sci U S A 1987;84(2);393-7. PMID: 3540965
De07: De Mey M, Lequeux GJ, Beauprez JJ, Maertens J, Van Horen E, Soetaert WK, Vanrolleghem PA, Vandamme EJ (2007). "Comparison of different strategies to reduce acetate formation in Escherichia coli." Biotechnol Prog 23(5);1053-63. PMID: 17715942
DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114
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